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1.  Clinical importance and surgical decision-making regarding proximal resection margin for gastric cancer 
Because of the intramural spread of gastric cancer, a sufficient length of a resection margin has to be attained to ensure complete excision of the tumor. There has been debate on an adequate length of proximal resection margin (PRM) and its related issues. Thus, the objective of this article is to review several studies on PRM and to summarize the current evidence on the subject. Although there is some discrepancy in the recommended values for PRM between authors, a PRM of more than 2-3 cm for early gastric cancer and 5-6 cm for advanced gastric cancer is thought to be acceptable. Once the margin is confirmed to be clear, however, the length of PRM measured in postoperative pathologic examination does not affect the patient’s survival, even when it is shorter than the recommended values. Hence, the recommendations for PRM length should be applied only to intraoperative decision-making to prevent positive margins on the final pathology. Given that a negative resection margin is the ultimate goal of determining an adequate PRM, development and improvement of reliable methods to confirm a negative resection margin intraoperatively would minimize the extent of surgery and offer a better quality of life to more patients. In the same context, special attention has to be paid to patients who have advanced stage or diffuse-type gastric cancer, because they are more likely to have a positive margin. Therefore, a wider excision with intraoperative frozen section (IFS) examination of the resection margin is necessary. Despite all the attempts to avoid positive margins, there is still a certain rate of positive-margin cases. Since the negative impact of a positive margin on prognosis is mostly obvious in low N stage patients, aggressive further management, such as extensive re-operation, is required for these patients. In conclusion, every possible preoperative and intraoperative evaluation should be thoroughly carried out to identify in advance the patients with a high risk of having positive margins; these patients need careful management with a wider excision or an IFS examination to confirm a negative margin during surgery.
doi:10.4251/wjgo.v5.i1.4
PMCID: PMC3671068  PMID: 23738049
Resection margin; Proximal resection margin; Negative resection margin; Positive resection margin; Gastrectomy; Gastric cancer
2.  Current status of robot-assisted gastric surgery 
In an effort to minimize the limitations of laparoscopy, a robotic surgery system was introduced, but its role for gastric cancer is still unclear. The objective of this article is to assess the current status of robotic surgery for gastric cancer and to predict future prospects. Although the current study was limited by its small number of patients and retrospective nature, robot-assisted gastrectomy with lymphadenectomy for the treatment of gastric cancer is a feasible and safe procedure for experienced laparoscopic surgeons. Most studies have reported satisfactory results for postoperative short-term coutcomes, such as: postoperative oral feeding, gas out, hospital stay and complications, compared with laparoscopic surgery; the difference is a longer operation time. However, robotic surgery showed a shallow learning curve compared with the familarity of conventional open surgery; after the accumulation of several cases, robotic surgery could be expected to result in a similar operation time. Robotic-assisted gastrectomy can expand the indications of minimally invasive surgery to include advanced gastric cancer by improving the ability to perform lymphadenectomy. Moreover, ”total” robotic gastrectomy can be facilitated using a robot-sewing technique and gastric submucosal tumors near the gastroesophageal junction or pylorus can be resected safely by this novel technique. In conclusion, robot-assisted gastrectomy may offer a good alternative to conventional open or laparoscopic surgery for gastric cancer, provided that long-term oncologic outcomes can be confirmed.
doi:10.4251/wjgo.v3.i10.137
PMCID: PMC3205112  PMID: 22046490
Robot surgery; Stomach; Minimally invasive surgery
3.  A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation 
World Journal of Gastroenterology : WJG  2014;20(35):12687-12690.
Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia. Clostridium difficile infection (CDI) is a common nosocomial diarrheal disease. Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI. The use of broad-spectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome. Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI. Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.
doi:10.3748/wjg.v20.i35.12687
PMCID: PMC4168110  PMID: 25253977
Clostridium difficile infection; Acute respiratory distress syndrome; Fecal microbiota transplantation
4.  Primary Pulmonary Plasmacytoma Presenting as Multiple Lung Nodules 
doi:10.3904/kjim.2012.27.1.111
PMCID: PMC3295978  PMID: 22403510
Plasmacytoma; Multiple Pulmonary Nodules; Paraproteinemias
6.  Aging over 70 Years Is Not a Decisively Dismal Prognostic Factor in Gastric Cancer Surgery 
Journal of Gastric Cancer  2011;11(4):200-205.
Purpose
Gastric cancer has a high incidence and mortality rate in Korea. Despite a growing older population and an increase in the number of older patients with gastric cancer, the older patients are not willing to undergo surgery due to their operative risks. Hence, to determine the clinical characteristics and outcomes of gastric cancer surgery for them, we investigate factors influencing the treatment decision.
Materials and Methods
Between January 1996 and December 2005, a total of 1,519 patients were classified into two groups; the younger age group between 41 and 69 years of age, and the older age group of 70 years or older. The analysis conducted included patient characteristics, accompanying disorders, related American Society of Anesthesiologists (ASA) grade, pathological characteristics and survival rate for each age group.
Results
Significant differences were found in the ASA grade (P<0.001) and the number of accompanying disorders (P<0.001) between the two groups. The average length of hospital stay after surgery was 14.5 days in the younger age group, and 13.3 days in the older age group (P=0.065). The average survival time was 47.5 months in the younger age group, and 43.2 months in the older age group (P<0.001).
Conclusions
This study demonstrated that there was more number of accompanying disorders with a high surgical risk in the older age group. However, there was no significant difference between the older and younger age groups in terms of the incidence of complications, under the given disease conditions and if proper management was provided.
doi:10.5230/jgc.2011.11.4.200
PMCID: PMC3273689  PMID: 22324010
Stomach neoplasms; Aged; Survival
7.  Cystic Brunner’s gland hamartoma in the duodenum: A case report 
Cystic Brunner’s gland hamartoma in the duodenum is exceedingly rare, although microscopic examination may sometimes reveal a Brunner’s gland hamartoma containing dilated ducts in the duodenum. We present a case of large cystic Brunner’s gland hamartoma in the duodenum with a long stalk, which is described in light of multidetector-row computed tomography, magnetic resonance imaging, and a modified small bowel series, together with pathologic correlation and differential diagnosis.
doi:10.3748/wjg.15.4980
PMCID: PMC2764981  PMID: 19842234
Brunner’s gland; Hamartoma; Duodenum; Multidetector-row computed tomography; Magnetic resonance imaging
8.  Multiple malignant extragastrointestinal stromal tumors of the greater omentum and results of immunohistochemistry and mutation analysis: A case report 
To report an extragastrointestinal stromal tumor (EGIST) that occurs outside the gastrointestinal tract and shows unique clinicopathologic and immunohistochemical features. In our case, we experienced multiple soft tissue tumors that originate primarily in the greater omentum, and in immunohistochemical analysis, the tumors showed features that correspond to malignant EGIST. Two large omental masses measured 15 cm x 10 cm and 5 cm × 4 cm sized and several small ovoid fragments were attached to small intestine, mesentery and peritoneum. On histologic findings, the masses were separated from small bowel serosa and had high mitotic count (115/50 HPFs). In the results of immunohistochemical stains, the tumor showed CD117 (c-kit) positive reactivity and high Ki-67 labeling index. On mutation analysis, the c-kit gene mutation was found in the juxtamembrane domain (exon 11) and it was heterozygote. Platelet-derived growth factor receptor (PDGFR) gene mutation was also found in the juxtamemembrane (exon 12) and it was polymorphism. From above findings, we proposed that there may be several mutational pathways to malignant EGIST, so further investigations could be needed to approach this unfavorable disease entity.
doi:10.3748/wjg.v13.i24.3392
PMCID: PMC4172724  PMID: 17659683
Extragastrointestinal stromal tumor; Greater omentum; c-kit; Platelet-derived growth factor receptor; Mutation
9.  Clinical Significance of Aberrant Wnt7a Promoter Methylation in Human Non-Small Cell Lung Cancer in Koreans 
Journal of Korean Medical Science  2015;30(2):155-161.
The Wnt signaling pathway has regulatory roles in cell proliferation, differentiation, and polarity. Aberrant Wnt pathway regulation can lead to abnormal cell proliferation and cancer, and loss of Wnt7a expression has been demonstrated in lung cancer cell lines. E-cadherin keeps intercellular integrity and prevents metastasis. Therefore, E-cadherin has been known as a prognostic factor in cancer. In the present study, we investigated the E-cadherin expression status by immunohistochemical stain and the Wnt7a promoter methylation status in human non-small cell lung carcinoma (NSCLC) by methylation-specific PCR. We also analyzed their correlations with clinicopathological factors. Methylation of the Wnt7a gene promoter was detected in the lung tissues of 32 of 121 (26.4%) patients with NSCLC. Wnt7a promoter methylation was correlated with advanced tumor stage (P = 0.036) and distant metastasis (P = 0.037). In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001). However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit. Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.
Graphical Abstract
doi:10.3346/jkms.2015.30.2.155
PMCID: PMC4310941  PMID: 25653486
Carcinoma, Non-small Cell Lung; Wnt7a; Biologic Markers; E-cadherin
10.  Superoxide Dismutase Gene (SOD1, SOD2, and SOD3) Polymorphisms and Antituberculosis Drug-induced Hepatitis 
Purpose
Drug-induced liver injury (DILI) is a serious issue often leading to discontinuation of the proper regimen of antituberculosis drugs (ATD). Previous studies have suggested that antioxidant enzymes play an important role in DILI.
Methods
We explored whether polymorphisms in superoxide dismutase genes, including Cu/Zn superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2) and extracellular superoxide dismutase (SOD3) are associated with ATD-induced hepatitis. Genotype distributions of four single nucleotide polymorphisms (SNPs) in three genes (rs2070424, SOD1; rs4880, SOD2; rs2536512, and rs1799895, SOD3) were compared between 84 patients with ATD-induced hepatitis and 237 patients tolerant to ATD.
Results
Intron SNP rs2070424 of SOD1 showed a significant association with ATD-induced hepatitis. The frequency of genotypes carrying minor alleles (GA or GG) was significantly higher in the case group than that of controls (P=0.019, OR=2.26, 95% CI 1.14-4.49). For the other SNPs of SOD2 and SOD3, there were no differences in genotype frequencies between ATD-induced hepatitis and ATD-tolerant controls.
Conclusions
These findings suggest that rs2070424 of SOD1 is significantly associated with ATD-induced hepatitis. This genetic variant may be a risk factor for ATD-induced hepatitis in individuals from Korea.
doi:10.4168/aair.2015.7.1.88
PMCID: PMC4274475  PMID: 25553268
Antituberculosis drugs; hepatitis; superoxide dismutase; polymorphism
11.  Primary Gastric Malignant Melanoma Mimicking Adenocarcinoma 
Journal of Gastric Cancer  2014;14(4):279-283.
We report a case of primary gastric malignant melanoma that was diagnosed after curative resection but initially misdiagnosed as adenocarcinoma. A 68-year-old woman was referred to our department for surgery for gastric adenocarcinoma presenting as a polypoid lesion with central ulceration located in the upper body of the stomach. The preoperative diagnosis was confirmed by endoscopic biopsy. We performed laparoscopic total gastrectomy, and the final pathologic evaluation led to the diagnosis of primary gastric malignant melanoma without a primary lesion detected in the body. To the best of our knowledge, primary gastric malignant melanoma is extremely rare, and this is the first case reported in our country. According to the literature, it has aggressive biologic activity compared with adenocarcinoma, and curative resection is the only promising treatment strategy. In our case, the patient received an early diagnosis and underwent curative gastrectomy with radical lymphadenectomy, and no recurrence was noted for about two years.
doi:10.5230/jgc.2014.14.4.279
PMCID: PMC4286909  PMID: 25580362
Melanoma; Stomach; Primary malignant
12.  The effects of secondhand smoke on chronic obstructive pulmonary disease in nonsmoking Korean adults 
Background/Aims
Smoking is widely acknowledged as the single most important risk factor for chronic obstructive pulmonary disease (COPD). However, the risk of COPD in nonsmokers exposed to secondhand smoke remains controversial. In this study, we investigated the association of secondhand smoke exposure with COPD prevalence in nonsmokers who reported never smoking.
Methods
This study was based on data obtained from the Korean National Health and Nutrition Examination Surveys (KNHANES) conducted from 2008 to 2010. Using nationwide stratified random sampling, 8,596 participants aged ≥ 40 years of age with available spirometry results were recruited. After selecting participants who never smoked, the duration of exposure to secondhand smoke was assessed based on the KNHANES questionnaire.
Results
The prevalence of COPD was 6.67% in participants who never smoked. We divided the participants who had never smoked into those with or without exposure to secondhand smoke. The group exposed to secondhand smoke was younger with less history of asthma and tuberculosis, higher income, and higher educational status. Multivariate logistic regression analysis determined that secondhand smoke did not increase the prevalence of COPD.
Conclusions
There was no significant difference in the prevalence of COPD between participants who had never smoked with or without exposure to secondhand smoke in our study. Thus, secondhand smoke may not be an important risk factor for the development of COPD in patients who have never smoked.
doi:10.3904/kjim.2014.29.5.613
PMCID: PMC4164725  PMID: 25228837
Never smoker; Secondhand smoke; Chronic obstructive pulmonary disease
13.  Fatal Clinical Course of Probable Invasive Pulmonary Aspergillosis with Influenza B Infection in an Immunocompetent Patient 
Invasive pulmonary aspergillosis (IPA) is rarely reported in patients who have normal immune function. Recently, IPA risk was reported in nonimmunocompromised hosts, such as patients with chronic obstructive pulmonary disease and critically ill patients in intensive care units. Moreover, influenza infection is also believed to be associated with IPA among immunocompetent patients. However, most reports on IPA with influenza A infection, including pandemic influenza H1N1, and IPA associated with influenza B infection were scarcely reported. Here, we report probable IPA with a fatal clinical course in an immunocompetent patient with influenza B infection. We demonstrate IPA as a possible complication in immunocompetent patients with influenza B infection. Early clinical suspicion of IPA and timely antifungal therapy are required for better outcomes in such cases.
doi:10.4046/trd.2014.77.3.141
PMCID: PMC4192313  PMID: 25309610
Invasive Pulmonary Aspergillosis; Influenza B Virus; Immunocompetence
14.  The Impact of Lifestyle Behaviors on the Acquisition of Pandemic (H1N1) Influenza Infection: A Case-Control Study 
Yonsei Medical Journal  2014;55(2):422-427.
Purpose
The purpose of this study was to evaluate the effects of lifestyle behaviors and health habits on the risk for acquiring pandemic influenza (H1N1) virus infection.
Materials and Methods
We conducted a case-control study in a secondary care hospital in South Korea between November 2009 and August 2010. We enrolled patients with H1N1 infection, as confirmed by a positive result of the real-time reverse transcriptase polymerase chain reaction assay; for each patient, we enrolled 4 age- and gender-matched controls with no history of H1N1 infection or severe acute respiratory illness during the H1N1 pandemic in South Korea (1:4 match).
Results
During the study period, 33 cases and 132 age- and gender-matched controls were enrolled. The case group had a higher percentage of current smokers (p<0.01), fewer subjects reporting regular physical activity (p=0.03), or regular vitamin supplementation (p<0.01), and more subjects reporting a higher annual incidence of the common cold (p=0.048) as compared to the control group. In the multivariable analysis, 2 factors were independently associated with the acquisition of H1N1 infection: current smoking [adjusted odds ratio (OR)=5.53; 95% confidence interval (CI), 1.60-19.16; p<0.01] and a higher annual incidence of the common cold (adjusted OR=1.24; 95% CI, 1.002-1.53; p=0.048).
Conclusion
A current smoking status and a history of frequent colds were associated with an increased risk of acquiring H1N1 infection.
doi:10.3349/ymj.2014.55.2.422
PMCID: PMC3936633  PMID: 24532513
Influenza A virus; H1N1 subtype; life style; smoking
15.  The Extended Rapid Response System: 1-Year Experience in a University Hospital 
Journal of Korean Medical Science  2014;29(3):423-430.
The rapid response system (RRS) is an innovative system designed for in-hospital, at-risk patients but underutilization of the RRS generally results in unexpected cardiopulmonary arrests. We implemented an extended RRS (E-RRS) that was triggered by actively screening at-risk patients prior to calls from primary medical attendants. These patients were identified from laboratory data, emergency consults, and step-down units. A four-member rapid response team was assembled that included an ICU staff, and the team visited the patients more than twice per day for evaluation, triage, and treatment of the patients with evidence of acute physiological decline. The goal was to provide this treatment before the team received a call from the patient's primary physician. We sought to describe the effectiveness of the E-RRS at preventing sudden and unexpected arrests and in-hospital mortality. Over the 1-yr intervention period, 2,722 patients were screened by the E-RRS program from 28,661 admissions. There were a total of 1,996 E-RRS activations of simple consultations for invasive procedures. After E-RRS implementation, the mean hospital code rate decreased by 31.1% and the mean in-hospital mortality rate was reduced by 15.3%. In conclusion, the implementation of E-RRS is associated with a reduction in the in-hospital code and mortality rates.
Graphical Abstract
doi:10.3346/jkms.2014.29.3.423
PMCID: PMC3945140  PMID: 24616594
Rapid Response System; Implementation; Extended RRS; At-Risk Patient; Death, Sudden, Cardiac; Mortality
16.  Surgical extraction of mandibular third molar in pterygomandibular space: a case report 
Impacted mandibular third molars are located between the second mandibular molar and mandibular ramus. However, ectopic mandibular third molars with heterotopic positions are reported in the subcondylar or pterygomandibular space. The usual cause of malposition is a cyst or tumor, and malposition without a pathology is rare. This case report described an impacted mandibular third molar in the pterygomandibular space without any associated pathology.
doi:10.5125/jkaoms.2013.39.5.242
PMCID: PMC3858136  PMID: 24471052
Third molar; Pterygomandibular space
17.  The stromal factors SDF1α, sFRP1 and VEGFD induce dopaminergic neuron differentiation of human pluripotent stem cells 
Journal of Neuroscience Research  2012;90(7):1367-1381.
Human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons hold potential for treating Parkinson’s disease (PD) through cell replacement therapy. Generation of DA neurons from hESCs has been achieved by co-culture with the stromal cell line PA6, a source of stromal cell-derived inducing activity (SDIA). However, the factor(s) produced by stromal cells that constitute SDIA are largely undefined. We previously reported that medium conditioned by PA6 cells can generate functional DA neurons from NTera2 human embryonal carcinoma stem cells. Here we show that PA6-conditioned medium can induce DA neuronal differentiation in both NTera2 cells and the hESC I6 cell line. To identify the factor(s) responsible for SDIA, we used large-scale microarray analysis of gene expression combined with mass spectrometric analysis of PA6-conditioned medium (CM). The candidate factors, hepatocyte growth factor (HGF), stromal cell-derived factor-1 α (SDF1α), secreted frizzled-related protein 1 (sFRP1), and vascular endothelial growth factor D (VEGFD) were identified and their concentrations in PA6 CM were established by immunoaffinity capillary electrophoresis. Upon addition of SDF1α, sFRP1 and VEGFD to the culture medium we observed an increase in the number of cells expressing tyrosine hydroxylase (a marker for DA neurons) and beta-III tubulin (a marker for immature neurons) in both the NTera2 and I6 cell lines. These results indicate that SDF1α, sFRP1 and VEGFD are major components of SDIA, and suggest the potential use of these defined factors to elicit DA differentiation of pluripotent human stem cells for therapeutic intervention in PD.
doi:10.1002/jnr.23064
PMCID: PMC3350575  PMID: 22535492
dopaminergic neurons; neuronal differentiation; stromal cell derived inducing activity; embryonic stem cells
18.  Effective correction of experimental errors in quantitative proteomics using stable isotope labeling by amino acids in cell culture (SILAC) 
Journal of Proteomics  2012;75(12):3720-3732.
Accurate and reliable quantitative proteomics in cell culture has been considerably facilitated by the introduction of the stable isotope labeling by amino acids in cell culture (SILAC), combined with high resolution mass spectrometry. There are however several major sources of quantification errors that commonly occur with SILAC techniques, i.e. incomplete incorporation of isotopic amino acids, arginine-to-proline conversion, and experimental errors in final sample mixing. Dataset normalization is a widely adopted solution to such errors, however this may not completely prevent introducing incorrect expression ratios. Here we demonstrate that a label-swap replication of SILAC experiments was able to effectively correct experimental errors by averaging ratios measured in individual replicates using quantitative proteomics and phosphoproteomics of ligand treatment of neural cell cultures. Furthermore, this strategy was successfully applied to a SILAC triplet experiment, which presents a much more complicated experimental matrix, affected by both incomplete labeling and arginine-to-proline conversion. Based on our results, we suggest that SILAC experiments should be designed to incorporate label-swap replications for enhanced reliability in expression ratios.
doi:10.1016/j.jprot.2012.04.035
PMCID: PMC3394155  PMID: 22575385
SILAC; incomplete isotope labeling; arginine-to-proline conversion; label-swap replication; receptor
19.  Cerebral Air Embolism Following Pigtail Catheter Insertion for Pleural Fluid Drainage 
Pigtail catheter drainage is a common procedure for the treatment of pleural effusion and pneumothorax. The most common complications of pigtail catheter insertion are pneumothorax, hemorrhage and chest pains. Cerebral air embolism is rare, but often fatal. In this paper, we report a case of cerebral air embolism in association with the insertion of a pigtail catheter for the drainage of a pleural effusion. A 67-year-old man is being presented with dyspnea, cough and right-side chest pains and was administered antibiotics for the treatment of pneumonia. The pneumonia failed to resolve and a loculated parapneumonic pleural effusion developed. A pigtail catheter was inserted in order to drain the pleural effusion, which resulted in cerebral air embolism. The patient was administered high-flow oxygen therapy and recovered without any neurologic complications.
doi:10.4046/trd.2013.74.6.286
PMCID: PMC3695312  PMID: 23814602
Embolism, Air; Chest Tubes; Pleural Effusion
20.  Incidence and Risk Factors of Contrast-Induced Nephropathy after Bronchial Arteriography or Bronchial Artery Embolization 
Background
In uncontrolled hemoptysis patient, bronchial arteriography and bronchial artery embolization (BAE) is a important procedure in diagnosis and treatment. The aim of this study is to assess the incidence of contrast-induced nephropathy and the risk factors of contrast-induced nephropathy (CIN) after bronchial arteriography and BAE.
Methods
We retrospectively reviewed the medical records of the patients who underwent bronchial arteriography and BAE in two university hospitals from January 2003 to December 2011. CIN was defined as rise of serum creatinine more than 25% of baseline value or 0.5 mg/dL at between 48 hours and 96 hours after bronchial arteriography and BAE. We excluded patients who already had severe renal insufficiency (serum creatinine≥4.0) or had been receiving dialysis.
Results
Of the total 100 screened patients, 88 patients met the enrollment criteria. CIN developed in 7 patients (8.0%). The mean duration between the exposure and development of CIN was 2.35±0.81 days. By using multivariate analysis, serum albumin level was found to be significantly associated with the development of CIN (p=0.0219).
Conclusion
These findings suggest that the incidence of CIN was higher than expected and patients with hypoalbuminemia should be monitored more carefully to prevent the development of CIN after bronchial arteriography and BAE.
doi:10.4046/trd.2013.74.4.163
PMCID: PMC3651926  PMID: 23678357
Contrast Media; Acute Kidney Injury; Bronchial Arteries; Embolization, Therapeutic
21.  TIARA genome database: update 2013 
The Total Integrated Archive of short-Read and Array (TIARA; http://tiara.gmi.ac.kr) database stores and integrates human genome data generated from multiple technologies including next-generation sequencing and high-resolution comparative genomic hybridization array. The TIARA genome browser is a powerful tool for the analysis of personal genomic information by exploring genomic variants such as SNPs, indels and structural variants simultaneously. As of September 2012, the TIARA database provides raw data and variant information for 13 sequenced whole genomes, 16 sequenced transcriptomes and 33 high resolution array assays. Sequencing reads are available at a depth of ∼30× for whole genomes and 50× for transcriptomes. Information on genomic variants includes a total of ∼9.56 million SNPs, 23 025 of which are non-synonymous SNPs, and ∼1.19 million indels. In this update, by adding high coverage sequencing of additional human individuals, the TIARA genome database now provides an extensive record of rare variants in humans. Following TIARA’s fundamentally integrative approach, new transcriptome sequencing data are matched with whole-genome sequencing data in the genome browser. Users can here observe, for example, the expression levels of human genes with allele-specific quantification. Improvements to the TIARA genome browser include the intuitive display of new complex and large-scale data sets.
doi:10.1093/database/bat003
PMCID: PMC3602786  PMID: 23515433
22.  Clinical Effects of Gemifloxacin on the Delay of Tuberculosis Treatment 
Journal of Korean Medical Science  2013;28(3):378-382.
Although gemifloxacin has low in vitro activity against Mycobacterium tuberculosis, the effect of gemifloxacin on the delay of tuberculosis (TB) treatment has not been validated in a clinical setting. The study group included patients with culture-confirmed pulmonary TB who initially received gemifloxacin for suspected community-acquired pneumonia (CAP). Two control groups contained patients treated with other fluoroquinolones or nonfluoroquinolone antibiotics. Sixteen cases were treated with gemifloxacin for suspected CAP before TB diagnosis. Sixteen and 32 patients were treated with other fluoroquinolones and nonfluoroquinolones, respectively. The median period from the initiation of antibiotics to the administration of anti-TB medication was nine days in the gemifloxacin group, which was significantly different from the other fluoroquinolones group (35 days). The median times for the nonfluoroquinolone group and the gemifloxacin group were not significantly different. There were no significant differences between the gemifloxacin and other fluoroquinolone group in terms of symptomatic and radiographic improvements. However, the frequency of radiographic improvement in the other fluoroquinolones group tended to be higher than in the gemifloxacin group. Gemifloxacin might be the preferred fluoroquinolone for treating CAP, to alleviate any concerns about delaying TB treatment.
doi:10.3346/jkms.2013.28.3.378
PMCID: PMC3594600  PMID: 23486643
Fluoroquinolones; Tuberculosis; Pneumonia
23.  Growth Inhibition by miR-519 via Multiple p21-Inducing Pathways 
Molecular and Cellular Biology  2012;32(13):2530-2548.
The microRNA miR-519 robustly inhibits cell proliferation, in turn triggering senescence and decreasing tumor growth. However, the molecular mediators of miR-519-elicited growth inhibition are unknown. Here, we systematically investigated the influence of miR-519 on gene expression profiles leading to growth cessation in HeLa human cervical carcinoma cells. By analyzing miR-519-triggered changes in protein and mRNA expression patterns and by identifying mRNAs associated with biotinylated miR-519, we uncovered two prominent subsets of miR-519-regulated mRNAs. One subset of miR-519 target mRNAs encoded DNA maintenance proteins (including DUT1, EXO1, RPA2, and POLE4); miR-519 repressed their expression and increased DNA damage, in turn raising the levels of the cyclin-dependent kinase (cdk) inhibitor p21. The other subset of miR-519 target mRNAs encoded proteins that control intracellular calcium levels (notably, ATP2C1 and ORAI1); their downregulation by miR-519 aberrantly elevated levels of cytosolic [Ca2+] storage in HeLa cells, similarly increasing p21 levels in a manner dependent on the Ca2+-activated kinases CaMKII and GSK3β. The rises in levels of DNA damage, the Ca2+ concentration, and p21 levels stimulated an autophagic phenotype in HeLa and other human carcinoma cell lines. As a consequence, ATP levels increased, and the level of activity of the AMP-activated protein kinase (AMPK) declined, further contributing to the elevation in the abundance of p21. Our results indicate that miR-519 promotes DNA damage, alters Ca2+ homeostasis, and enhances energy production; together, these processes elevate the expression level of p21, promoting growth inhibition and cell survival.
doi:10.1128/MCB.00510-12
PMCID: PMC3434494  PMID: 22547681
24.  Expression of Intercellular Adhesion Molecule-1 and E-Selectin in Gastric Cancer and Their Clinical Significance 
Journal of Gastric Cancer  2012;12(3):140-148.
Purpose
Among cell adhesion molecules, serum levels of intercellular adhesion molecule-1 and E-selectin are known to be correlated with the metastatic potential of gastric cancer. In the present study, the authors investigated the expression of intercellular adhesion molecule-1 and E-selectin in gastric cancer tissues and cultured gastric cancer cells, and examined their clinical value in gastric cancer.
Materials and Methods
The protein was extracted from gastric cancer tissues and cultured gastric cancer cells (MKN-28 and Kato-III) and the expression of intercellular adhesion molecule-1 and E-selectin was examined by western blotting. The clinical significance of intercellular adhesion molecule-1 and E-selectin was explored, using immunohistochemical staining of specimens from 157 gastric cancer patients.
Results
In western blot analysis, the expressions of intercellular adhesion molecule-1 in gastric cancer tissues and cultured gastric cancer cells were increased, however, E-selectin in gastric cancer tissues and cells were not increased. Among 157 gastric cancer patients, 79 patients (50%) were intercellular adhesion molecule-1 positive and had larger tumor size, an increased depth of tumor invasion, lymph node metastasis and perineural invasion. The intercellular adhesion molecule-1 positive group showed a higher incidence of tumor recurrence (40.5%), and a poorer 3-year survival than the negative group (54.9 vs. 85.9%, respectively).
Conclusions
Intercellular adhesion molecule-1 is overexpressed in gastric cancer tissues and cultured gastric cancer cells, whereas E-selectin is not overexpressed. Increased expression of intercellular adhesion molecule-1 in gastric cancer could be related to the aggressive nature of the tumor, and has a poor prognostic effect on gastric cancer.
doi:10.5230/jgc.2012.12.3.140
PMCID: PMC3473220  PMID: 23094225
Stomach neoplasms; Intercellular adhesion molecule-1; E-selectin
25.  Metabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventions 
The hypothalamus is an essential relay in the neural circuitry underlying energy metabolism that needs to continually adapt to changes in the energetic environment. The neuroendocrine control of food intake and energy expenditure is associated with, and likely dependent upon, hypothalamic plasticity. Severe disturbances in energy metabolism, such as those that occur in obesity, are therefore likely to be associated with disruption of hypothalamic transcriptomic plasticity. In this paper, we investigated the effects of two well-characterized antiaging interventions, caloric restriction and voluntary wheel running, in two distinct physiological paradigms, that is, diabetic (db/db) and nondiabetic wild-type (C57/Bl/6) animals to investigate the contextual sensitivity of hypothalamic transcriptomic responses. We found that, both quantitatively and qualitatively, caloric restriction and physical exercise were associated with distinct transcriptional signatures that differed significantly between diabetic and non-diabetic mice. This suggests that challenges to metabolic homeostasis regulate distinct hypothalamic gene sets in diabetic and non-diabetic animals. A greater understanding of how genetic background contributes to hypothalamic response mechanisms could pave the way for the development of more nuanced therapeutics for the treatment of metabolic disorders that occur in diverse physiological backgrounds.
doi:10.1155/2012/732975
PMCID: PMC3427989  PMID: 22934110

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